On November 1, 2023 Corvus Pharmaceuticals, Inc. (Nasdaq: CRVS), a clinical-stage biopharmaceutical company, reported the publication of preclinical data that demonstrated the potential of ITK inhibition as a novel approach to treat T cell-mediated inflammatory and immune diseases (Press release, Corvus Pharmaceuticals, NOV 1, 2023, View Source [SID1234636630]). Corvus’ ITK inhibitors include soquelitinib (formerly known as CPI-818), which was used in the preclinical studies and is currently in clinical trials for oncology indications, and several next-generation molecules that are being optimized for use in a variety of inflammatory and immune disease indications.
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"Our research on soquelitinib and selective ITK inhibition is uncovering valuable new information about immune function and the role of ITK in different diseases," said James Rosenbaum, M.D., senior vice president of research at Corvus. "The activity of soquelitinib in various inflammatory and immune disease models highlights the essential role of ITK in multiple T cell functions. Our publication demonstrates that soquelitinib can impact disease-associated cytokines by targeting the cellular sources, specifically Th2 and Th17 cells, which produce cytokines like IL-4, IL-5, IL-13 and IL-17. We believe that blocking the source of cytokine production upstream offers advantages over existing therapies that individually target specific cytokines."
Professor Yannick Allanore, M.D., Ph.D., Professor of Rheumatology, Université Paris Cité, Institut Cochin, Paris, France, and a co-author of the publication, said, "Pulmonary fibrosis and systemic sclerosis are often fatal diseases for which current therapy is inadequate. Soquelitinib utilizes a novel mechanism and was effective in our model related to systemic sclerosis which is based on Fra2 gene overexpression, a model designed to represent human lung disease manifestations. Based on these data, we are eager to evaluate soquelitinib in a clinical trial for fibrotic diseases."
The publication, entitled "Soquelitinib, A Selective Inhibitor of Interleukin- 2- Inducible T Cell Kinase (ITK), is Active in Several Murine Models of T Cell-Mediated Inflammatory Disease," highlights data demonstrating that soquelitinib was active in six different models of T cell-mediated inflammatory and immune disease, including acute and chronic asthma, pulmonary fibrosis, systemic sclerosis (scleroderma), psoriasis, and acute graft versus host disease. The data also describe soquelitinib’s unique mechanism of action, providing rationale for the development of ITK inhibition in a range of additional Th2 and Th17 mediated diseases, including asthma, psoriasis, atopic dermatitis, chronic obstructive pulmonary disease (COPD), systemic sclerosis, lupus and other diseases. The published research was a result of collaborations between scientists at Corvus and researchers at both Memorial Sloan Kettering Cancer Center in New York and The National Institute of Health and Medical Research (INSERM) in France. The publication is now available online as a preprint at bioRxiv.org and on the Publications and Presentations page of the Corvus website.
"We are making significant progress with soquelitinib and believe that Corvus is firmly positioned as a leader in the scientific and clinical development of ITK inhibition as a platform opportunity across cancer, inflammation and immune disease," said Richard A. Miller, M.D., co-founder, president, and CEO of Corvus. "Our primary focus is treating T cell lymphomas and cancer and we are actively preparing for a registrational Phase 3 trial of soquelitinib for peripheral T cell lymphoma. With this new publication, we further demonstrate the wide range of opportunities for ITK inhibition across specific indications with ongoing patient needs for new therapies. In addition, we have a robust pipeline of next generation ITK inhibitors and a portfolio of intellectual property that we believe provide attractive partnering opportunities for companies focused on various inflammatory and immune diseases."
Key results from the preclinical studies described in the publication demonstrated that soquelitinib had the following observed effects in models of inflammatory disease:
Acute and chronic asthma models:
Significant reductions in Th2 cytokines IL-4, IL-5 and IL-13 in both models, along with reductions in a validated disease activity score
Reduction in IL-6 signifying amelioration of inflammation
Systemic sclerosis (Fra2 gene overexpression) model:
Improvement in clinical score and preservation of body weight
Improvement in lung histology, reduction of fibrosis and improvement in pulmonary vascular hypertension
Reduction of GATA3-expressing T cells, indicative of effect on Th2 cells
Reduction of ROR gammaT cells (RORγT), indicative of effects on Th17 cells
Pulmonary fibrosis (bleomycin-induced) model:
More consistent reduction of pulmonary fibrosis compared to an FDA-approved medication (nintedanib)
Similar reduction in GATA3 as the systemic sclerosis model results
Reduction in MMP2 and TGF beta, two messenger RNAs associated with fibrosis
Psoriasis (imiquimod (IMQ)-induced) model:
Improvement in epidermal thickness, erosion and inflammation
In vitro studies demonstrated a reduction in the expression of RORγT protein, a master transcription factor that is responsible for developing Th17 cells, and a corresponding dose-dependent reduction in IL-17 cytokine production
Graft versus host disease (GVHD) model:
Improvement in survival rates and corresponding decrease in clinical GVHD score
No impact on engraftment or graft-versus-tumor effect